Research progress of myocardial scaffolds in the treatment of myocardial infarction / 中国组织工程研究

BACKGROUND: In recent years, myocardial tissue engineering has developed rapidly. By using exogenous biomaterials to simulate extracellular matrix, damaged myocardial cells can be effectively repaired or reconstructed, which has great potential value in the treatment of ischemic heart diseases such as myocardial infarction. OBJECTIVE: To review the research progress of myocardial scaffolds in the treatment of myocardial infarction. METHODS: NCBI and WanFang databases were retrieved for relevant articles published from 2008 to 2018, with the key words of "myocardial scaffold materials, myocardial infarction" in English and Chinese, respectively. RESULTS AND CONCLUSION: At present, the commonly used myocardial scaffolds are mainly natural biomaterials (including collagen/Matrigel, fibrin, chitosan, hyaluronic acid, and algae hydrochloric acid) , synthetic materials (polyester synthetic materials and nanomaterials) and composite scaffolds. Due to the complexity of cardiac environment and heart function, the selection of scaffold materials should fully take account of biocompatibility, immunogenicity, conductivity, degradation rate and susceptibility to ischemia and hypoxia. Although many scaffold designs have begun to meet many requirements, there are still many kinds of stent materials for clinical application. It is believed that with the further development of researchers and application tools, people can expect to create myocardial scaffolds close to the physiological function of the original tissue, so that the heart function can be better restored.

Study of hydrodynamic in vitro and animal experiment of a homebred pneumatic pulsatile ventricular assist device / 天津医药

Objective To study in vitro hydrodynamics of a pneumatic pulsatile ventricular assist device developed ex?clusively by China, and establish an animal model for the detection by the device. Methods The hydromechanics experi?ment was performed on an in vitro test loop using MEDOS-System to drive the ventricular assist device, and lycerl-water so?lution was used as circulating medium. The changes of afterload pressure and the output of the pump were monitored, and the impermeability and stability were also assessed after the experiment. Six adult dogs were used as the experimental animals. The device worked in the left heart assistance mode for 1 hour then the ventricular fibrillation was induced by potassium chloride, and then defibrillated after 5 min while the device remained working. The hemodynamics data were monitored con?secutively during the trial. Results The ventricular assist device worked stably and reliably during the hemodynamic exper?iment. The pump can generate more than 4 L/min flow against the afterload pressure of 100 mmHg. There were no significant changes in heart rate at different time points in experimental dogs after left ventricular assist. Comparison between after auxil?iary immediately and former auxiliary, the diastolic blood pressure of dogs increased 30 mmHg with the ventricular assist, and the diastolic pressure increased 19 mmHg. No obvious fluctuation in blood pressure was found during the auxiliary pro?cess. The diastolic blood pressure stayed at 60 mmHg when the heart was in ventricular fibrillation, and returned to normal after electrical defibrillation. Conclusion The ventricular assist device works stably in vitro test, and the pump can meet the need of adult’s ventricular assist. It is effective and security to dogs in short term. The effects of long-term use need to be future proved.

Biocompatibility of Ricinus communis polymer with addition of calcium carbonate compared to titanium. Experimental study in guinea pigs / Biocompatibilidade do polímero de óleo de mamona com acréscimo de carbonato de cálcio comparado ao titânio. Estudo experimental em cobaias.

Objective: The aim of the present investigation was to determine whether the difference in inflammatory tissue reaction between the Riccinus communis (castor) polymer with calcium carbonate and the titanium implant is statistically significant. Methods: Thirty-two Cavia porcellus were allocated into four groups of eight animals each. We implanted the two types of materials in the retroperitoneal space of all the animals. They were euthanized at 7, 20, 30 and 40 days after surgery, and an histological study of the samples was conducted. Results: All implants showed characteristics of chronic inflammation regardless of the material and timepoint of evaluation. There was no statistically significant difference between Pm+CaCO3 and Ti with regard to the presence of granulation tissue, tissue congestion, histiocytes, lymphocytes, neutrophils, giant cells, and fibrosis (P> 0.05). Conclusion: The castor oil polymer plus calcium carbonate implant was not statistically different from the titanium implant regarding inflammatory tissue reaction. .

Objetivo: Determinar se a reação tecidual do implante retroperitoneal do polímero de óleo de mamona com acréscimo de carbonato de cálcio (Pm+CaCO3) é significativa, por meio de análise histopatológica, tendo como controle o implante de titânio não tratado (Ti). Métodos: Estudo experimental, intervencionista e randomizado com 32 cobaias. Os animais foram separados em quatro grupos iguais e eutanasiados com 7, 20, 30 e 40 dias após o ato cirúrgico. Foram confeccionadas lâminas em hematoxilina-eosina e em tricrômio de Masson. Em relação a variáveis qualitativas dicotômicas, para análise da diferença entre o Pm+CaCO3 e o Ti em cada momento de avaliação foi usado o teste binomial. Considerando os materiais separadamente, a comparação dos quatro grupos foi feita utilizandose o teste exato de Fisher. Valores de P<0,05 indicaram significância estatística. Resultados: Todos os implantes apresentaram características de inflamação crônica, independente do material e do momento de avaliação. Não houve diferença estatisticamente significativa entre o Pm+CaCO3 e o Ti considerando a presença de tecido de granulação, congestão tecidual, histiócitos, linfócitos, neutrófilos, células gigantes e fibrose (P>0,05). Conclusão: Não foi encontrada diferença significativa entre a reação tecidual do Pm+CaCO3 e a do Ti. .

Asistencia ventricular sistémica con dispositivo HeartMate 2como puente al trasplante en la transposición corregida de los grandes vasos / Systemic Ventricular Assistance Using a HeartMate 2 Device as Bridge to Transplant in a Congenitally Corrected Transposition of the Great Vessels / Systemic ventricular assistance using a HeartMate 2 device as bridge to transplant in a congenitally corrected transposition of the great vessels

Merced a los continuos progresos en el tratamiento médico y quirúrgico, el número de pacientes adultos portadores de cardiopatías congénitas se encuentra en incremento, quienes con el paso del tiempo desarrollan diversas complicaciones, entre ellas insuficiencia cardíaca avanzada, la cual puede requerir terapéuticas como el trasplante cardíaco y en ocasiones plantea la necesidad del implante de un dispositivo de asistencia circulatoria, ya sea como puente al trasplante o como tratamiento definitivo. En esta presentación se describe un caso que ilustra la problemática de la población portadora de cardiopatías congénitas en el adulto. Se trata de un paciente de sexo masculino, de 41 años, portador de transposición corregida de los grandes vasos que desarrolló insuficiencia cardíaca avanzada del ventrículo morfológicamente derecho, el cual sostiene la circulación sistémica. Ante reiteradas descompensaciones bajo tratamiento médico, incluido el uso domiciliario de inotrópicos, se procedió al implante de un dispositivo de asistencia circulatoria inicialmente planteado como puente al trasplante. Tras diversas complicaciones posoperatorias, el paciente fue derivado a una institución de rehabilitación a la espera del trasplante.

Due to continuous advances in medical and surgical treatment, the large number of adult patients with congenital heart diseases is increasing; with the passing of time, these conditions develop several complications including advanced heart failure, which may require therapeutic approaches such as cardiac transplant and, in certain cases, the implantation of a circulatory support device, both as a bridge to transplant or as a definitive treatment. This report describes a case that shows the problem of the adult population with congenital heart disease. We present a 41 year-old male patient with congenitally corrected transposition of the great vessels who developed advanced heart failure of the morphologically right ventricle, which supports the systemic circulation. Due to several decompensations under medical treatment, including the home use of inotropes, a circulatory support device was implanted as an early bridge to transplant. After several postoperative complications, the patient was transferred to a rehabilitation center to wait for transplantation.

Biocompatibilidade do polímero da mamona comparada ao implante de titânio para corações artificiais: estudo experimental em cobaias / Biocompatibility of Ricinus comunnis polymer compared to titanium implant used in artificial hearts: experimental study in guinea pigs

OBJETIVO: Determinar se a reação tecidual do implante retroperitoneal do polímero de óleo de mamona (Pm) é significativa ou não por meio de análise histopatológica, tendo como controle o implante de titânio (Ti). MÉTODOS: Estudo experimental, intervencionista e randomizado com 32 cobaias. Os animais foram divididos em quatro grupos iguais e eutanasiados com 7, 20, 30 e 40 dias após o ato cirúrgico. Foram confeccionadas lâminas em hematoxilina-eosina e em tricrômio de Masson. Na comparação dos tipos de material em relação a variáveis quantitativas, foi considerado o teste não-paramétrico de Wilcoxon. Em relação a essas variáveis, os grupos definidos pelo dia do sacrifício foram comparados usando-se o teste não-paramétrico de Kruskal-Wallis. Os resultados obtidos no estudo da fibrose foram expressos por frequências e percentuais. Para a comparação entre os grupos definidos pelo dia do sacrifício, em relação a variáveis qualitativas dicotômicas da fibrose, foi considerado o teste exato de Fisher. Para avaliar a diferença entre os materiais titânio e polímero em cada grupo, ainda em se tratando da fibrose, foi considerado o teste binomial. Valores de P<0,05 indicaram significância estatística. RESULTADOS: A análise das variáveis quantitativas não demonstrou diferença nas reações teciduais entre os materiais (P>0,05). A análise da variável qualitativa também não demonstrou diferença entre as reações teciduais dos materiais (P>0,05). CONCLUSÃO: Não foi encontrada significância estatística entre a reação tecidual do Pm e do Ti.

OBJECTIVE: The aim of the present investigation is to determine if the tissue reaction to the Riccinus communis (mamona) polymer has significant statistical difference compared to the tissue reaction provoked by the titanium implant. METHODS: Thirty two Cavia porcellus were divided into four groups containing eight animals each one. We implanted the two types of materials in the retroperitoneal space of all the animals. They were sacrificed at 7, 20, 30 and 40 days after surgery and the samples were submitted to histological study. RESULTS: The quantitative analysis did not show difference between the tissue reaction of the two materials (P>0.05). The analysis of the qualitative variable also did not show difference between the tissue reaction of the materials (P>0.05). CONCLUSION: Macroscopic and microscopic results showed that the castor oil polymer implant has no significant statistical difference compared to the titanium implant tissue reaction.

Estudo experimental da aplicação do ventrículo artificial eletromecânico pulsátil implantável / Experimental study of pulsatile implantable electromechanical artificial ventricle

OBJETIVO: Apresentar os resultados da aplicação deste dispositivo em animais de experimentação, promovendo auxílio hemodinâmico apenas ao ventrículo esquerdo (VE). MÉTODOS: Entre junho 2002 e outubro 2009, foram implantados em 27 bezerros com idade 2½ a 4 meses e peso 80/100 kg e, por meio de anestesia geral e ventilação controlada e de toracotomia lateral esquerda, era introduzida cânula no ápice do VE e anastomose término/lateral de tubo vascular de politetrafluoretileno (PTFE) com a porção descendente da aorta torácica, ambos interligados ao dispositivo implantado no subcutâneo abaixo do diafragma (24) e intratorácico (três). Em cinco bezerros, o dispositivo foi aplicado com auxílio de circulação extracorpórea (CEC) e, em 22, sem CEC. RESULTADOS: Ocorreram dois óbitos durante o implante e três por causas diversas nas primeiras horas de pós-operatório (PO), sendo um relacionado ao dispositivo. A sobrevivência entre o 1º e 6º dia de PO ocorreu em 17 animais e entre o 8º e 31º dia de PO em cinco, com causas determinantes diversas, não só por problemas clínico/cirúrgicos, mas também relacionados ao dispositivo. O impacto hemodinâmico avaliado pela análise da pressão sistêmica mostrou incremento que variou de 20 a 40 mmHg e os dados laboratoriais analisados demonstraram baixos impactos traumáticos à crase sanguínea e boa biocompatibilidade. CONCLUSÃO: Trata-se de pesquisa árdua e complexa onde a cada experimento são identificados problemas não só de implantabilidade, mas também relacionados ao dispositivo, que vão sendo sistematicamente corrigidos, tornando-o cada vez mais seguro e eficaz.

OBJECTIVE: The objective is to present the results of the application this device in experimental animals unloading only the left ventricle. METHODS: Between June 2002 and October 2009, were implanted in 27 calfs with age between 2½ to 4 months and 80 to 100 kg of weight, with general anaesthesia and controled ventilation, by mean of left thoracotomy a cannula in the apex of VE and a lateral anastomose of a GTFE vascular graft tube in the descending portion of the thoracic aorta, both connected to the device implanted below the diaphragm in the subcutaneous (24) and intrathoracic (three). The cardiopulmonary bypass (BP) was used in five calves, and directly introduce the outflow cannula in 22. RESULTS: During the implant two and in the first hours of the post operative period (PO) three deaths were observed, one related to the device. The survival between the first and the six PO day was found in 17 calves and between day 8 and day 31 (PO) in five all caused by clinical/surgical problems, and related to the device. The hemodynamic impact by the systemic pressure analysis showed 20 to 40 mmHg increase and the laboratory parameters showed lower levels of traumatic impact to the blood and a good biocompatibility. CONCLUSIONS: This kind of research is arduous and complex where at each experiment many problems are indentified in the implantability and in the device, which are sistematic correct, to became device/procedure safe and effective.

Desempenho hemodinâmico e resposta inflamatória durante o uso do DAV-InCor como ponte para o transplante / Hemodynamic performance and inflammatory response during the use of VAD-InCor as a bridge to transplant

FUNDAMENTO: O transplante cardíaco enfrenta o grave problema da escassez de doadores. Estima-se que entre 20 por cento e 40 por cento dos pacientes falecem na fila de espera. Para esses pacientes, a utilização de dispositivos de assistência circulatória é, muitas vezes, a única possibilidade de sobrevivência durante a espera do doador. No Brasil, não existe nenhum programa regular de utilização desses dispositivos como ponte para transplante. OBJETIVO: Avaliar o desempenho hemodinâmico e a resposta inflamatória durante a utilização do DAV-InCor como ponte para transplante. MÉTODOS: Entre outubro de 2003 e abril de 2006, 11 pacientes, indicados em caráter de prioridade para o transplante cardíaco, evoluíram em choque cardiogênico refratário. O implante do DAV-InCor foi realizado em sete pacientes. O diagnóstico etiológico foi cardiopatia chagásica em cinco pacientes e cardiomiopatia dilatada idiopática em dois. RESULTADOS: A assistência mecânica ao ventrículo esquerdo foi mantida nos sete pacientes por períodos entre 14 e 42 dias (média 26,2). O desempenho hemodinâmico foi adequado, com a normalização do índice cardíaco, dos níveis de saturação venosa de O2 e do lactato. O transplante foi realizado em dois pacientes, os outros cinco faleceram por infecção sistêmica ou falência de múltiplos órgãos. CONCLUSÃO: O desempenho do DAV-Incor, no comportamento hemodinâmico dos pacientes estudados, foi adequado para a manutenção de uma condição circulatória satisfatória durante o período estudado. Houve melhora dos parâmetros de perfusão tecidual e manutenção de sinais de resposta inflamatória sistêmica. Houve alta incidência de complicações; contudo, não foram demonstradas complicações relacionadas ao dispositivo que comprometam a segurança da utilização do mesmo.

BACKGROUND: Cardiac transplantation faces the serious problem of lack of donors and it is estimated that 20 to 40 percent of the patients die while waiting for heart transplantation. For these patients, the use of mechanical circulatory assist devices is the only choice of survival while waiting for a donor. In Brazil, the experience with mechanical circulatory support is limited and there is no regular program regarding the use of these devices as a bridge to heart transplantation. OBJECTIVE: To evaluate the hemodynamic performance and the systemic inflammatory response during the clinical use of the InCor-type ventricular assist device (VAD-InCor) as a bridge to heart transplantation. METHODS: Between October 2003 and April 2006, 11 patients in the waiting list for heart transplantation presented hemodynamic deterioration due to refractory cardiogenic shock. Seven of these patients were submitted to VAD-InCor implantation for left ventricular assistance. The etiologic diagnosis was Chagas' disease in 5 patients and idiopathic dilated cardiomyopathy in 2. RESULTS: The duration of left ventricular assistance ranged from 14 to 42 days (mean 26.2 days). During this period, the hemodynamic performance of the DAV-InCor was adequate to support a normal hemodynamic state. There was normalization of central venous oxygen saturation and serum lactate. Two patients were submitted to heart transplantation, while the other 5 patients died under assistance due to infection and multiple organ failure. CONCLUSION: The performance of the VAD-InCor, in the hemodynamic behavior of the studied patients, was adequate for the maintenance of a satisfactory circulatory state during the studied period. There was improvement in the tissue perfusion parameters and maintenance of systemic inflammatory response signs. There was a high incidence of complications; however, complications related to the device, which could compromise the safety of its use, were not demonstrated.

Surgical Technique for Korean Artificial Heart(AnyHeart) Implantation Using a Right Thoracotomy Approach / 대한흉부외과학회지

BACKGROUND: The surgical technique for biventricular assist device(BVAD) implantation has mainly consisted of cannulation procedures. A median sternotomy has been the technique of choice as it gives a surgeon an excellent exposure of the heart. However, considering that most patients require a future sternotomy or already have a previous sternotomy, sternotomy-related complication remains a major concern in BVAD implantation. Based on this consideration as well as the clinical experiences of conventional heart surgery, the authors have hypothesized that the cardiac chambers for BVAD cannulation can be approached from the right side of the heart. The purpose of this study to develop a novel surgical technique of right thoracotomy for BVAD implantation in an animal study. MATERIAL AND METHOD: For last two years, 16 (11 calves, 3 canines, and 2 sheep) out of 30 experimental animals with AnyHeart implantation underwent a right thoracotomy. The device was used as an implantable BVAD in 14 animals, a wearable BVAD in 1, and an implantable LVAD in 1. The chest cavity was entered through the 4th intercostal space or the 5th periosteal bed. As for the BVAD use, a right inflow cannula was inserted into the right atrial free wall and a right outflow cannula was grafted onto the main pulmonary artery. A left inflow cannula was inserted into the interatrial groove and a left outflow cannula was grafted on the innominate artery of the ascending aorta. The connecting tubeswere brought out through the thoracotomy wound and connected to the pump located in the subcutaneous pocket at the right flank. RESULT: Except for the 5 animals for a fitting test or during the early learning curve, all recovered smoothly from the procedures. The inflow drainage allowed the pump output 6.5 L/min at the maximum with 3-3.5 L/min in an average. Of the survivors, there noted no procedure-related mortality or morbidity. Necropsy findings demonstrated the well-positioned cannula tips in the each cardiac chamber. CONCLUSION: The technique of right thoracotomy approach in AnyHeart implantation is simple, safe, and reproducible. As it can avoid sternotomy-orresternotomy-related complications, the authors suggest a right thoracotomy approach as one of the techniques for BVAD implantation. The technique would also be suggested as an alternatitve for a median sternotomy in a certain group of patients with various VAD implantations.

A Clinical Experience of Korean Artificial Heart(AnyHeart) / 대한흉부외과학회지

Korean artificial heart(AnyHeart) is a single-pieced and implantable bi-ventricular pulsatile pump adapting a moving actuator mechanism. The authors report a case of clinical application of AnyHeart as a life-saving device for the patients with end-stage heart disease combined with biventricular failure.

Application of th Total Artificial Heart as an Implantable Biventricular Assist Device by Left Thoracotomy in an Ovine Model / 대한흉부외과학회지

BACKGROUND: The purpose of this study was to investigate the possibility of using the moving-actuator type total artificial heart as a biventricular assist device(BVAD) and to establish a safe and effective animal model for the implantation of a BVAD. MATERIAL AND METHOD: Seven Corridale sheep were used in this study wherein left thoracotomy was performed. The left and right outflow cannulas were anastomosed to the descending thoracic aorta and the main pulmonary artery, and the left and right inflow cannulas were inserted to the left atrium and the right atrial appendage. The devices were positioned in the preperitoneal pocket in 4 sheep, in the left pleural cavity in 2 sheep, and externally in 1 sheep. The aPTT was maintained between the 2 and 2.5 times the range that of the baseline. RESULT: Cannulation was carried out successfully in all cases. There was no case of operative death or immediate postoperative death. Three sheep expired postoperatively on the 2nd day because of thromboembolism, an artificial ventilator accident, and device and respiratory failure. Three other sheep died postoperatively on the 4th day because of acute renal and respiratory failure following thromboembolism. One sheep survived for 28 days. Experimentation on this animal terminated due to an electrical short-circuit caused by motor wire erosion. Thrombi were found on the valves of 4 out of 7 animals, especially on the connection between valves and the device. However , there was no thrombus in the cannulas. CONCLUSION: In conclusion, left thoracotomy for insertion of 4 cannulas and placement of device in the preperitoneal space is the safe and effective operative technique in ovine for testing in-vivo biocompatibility of the BVAD. Furthermore, it may be possible to use a moving-actuator type total artificial heart as a BVAD if technical improvements for reducing thromboembolism are carried out.